Glioblastoma following treatment with fingolimod for relapsing-remitting multiple sclerosis

Abstract

Glioblastoma is a rare and aggressive primary brain tumor with incidence of 5 per 100,000 annually. We report a 50-year-old woman diagnosed with glioblastoma within 3 years of induction of fingolimod therapy for relapsing-remitting multiple sclerosis. Fingolimod, an immunomodulating agent used in the treatment of relapsing-remitting multiple sclerosis, has also been suggested to impart a cardioprotective role in heart failure and arrhythmia via activation of P21-activated kinase-1 (Pak1). In the brain, Pak1 activation has been shown to correlate with decreased survival time amongst patients with glioblastoma. A molecular mechanism underlying a link between fingolimod use and glioblastoma development may involve activation of Pak1. To our knowledge, this is the first report of a potential association between fingolimod use and glioblastoma development.

Engineering Novel Targeted Boron‐10‐Enriched Theranostic Nanomedicine to Combat against Murine Brain Tumors via MR Imaging‐Guided Boron Neutron Capture Therapy

“…The development of effective diagnostic and therapeutic treatment options for cancer is in high demand. Among the various types of cancers, glioblastoma multiforme (GBM) is a common malignant brain tumor in adults and is considered to be incurable in most patients, with a very poor survival rate . The treatment options available for combating GBMs include neurosurgery, chemotherapy, radiation therapy (RT), or a combination of multiple modalities .…”

A challenging case of concurrent multiple sclerosis and anaplastic astrocytoma

“…[23] However, despite the latter epigenetic traits, further studies are warranted to elucidate a plausible cause- effect scenario in this particular context. Therapeutic MS- immunomodulators such as Fingolimod have also been suggested to have the potential to develop glioblastomas through the activation of P21-activated kinase-1;[31] despite its proven clinical safety, one case of glioma was reported using azathioprine in a renal transplant recipient. [21] Cases of gliomas evolving from pharmacologic immunomodulators remain rare but suggest a possible environmental relationship between immunosuppression and malignant transformation.…”

“…Surgical intervention and microscopic evaluation are often necessary to ensure diagnosis;[1] in this specific context, cases of concurrent MS and gliomas have been described. [1,2,5,12,18,23,25,29,31] The origins of this type of coexistence (incidental or causal) remain a matter of debate; indeed, some of the reported theories include neoplastic changes taking place in areas of demyelination. [29] As illustrated by this case, access to modern radiology and reliable microscopic assessment at the time of diagnosis and follow-up remain crucial in terms of treatment optimization and prolonged survival.…”

New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

“…An increase in the concentration of NO causes the differentiation and stimulation of T reg function, which is as an important mechanism of the immunosuppressive effect of FTY720 on these cells. However, such an action can help facilitate the development of cancer [ 411 , 412 ].…”

“…Immune reactions also play a very important role in tackling cancer. The use of immunosuppressive drugs such as FTY720 results in the impairment of the immune system and consequently may facilitate the development of GBM as well as other tumors [ 411 , 412 ].…”